ESMO: Fentanyl Nasal Spray Quells Breakthrough Pain

Action Points

Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Discuss with patients that preliminary data from a recent study indicates that fentanyl nasal spray is effective in controlling 90% of episodes of breakthrough pain in cancer patients.

MILAN -- Fentanyl nasal spray controlled more than 90% of episodes of breakthrough pain in cancer patients -- without the need for rescue medication -- according to data from three phase III clinical trials.

The clinical trials, encompassing 500 patients, showed that the efficacy of intranasal fentanyl remained consistent across 16 weeks of use and more than 40,000 episodes of breakthrough pain, reported David Brooks, MD, of Chesterfield and North Derbyshire Royal Hospital in Chesterfield, England, and colleagues.

More than 80% of patients successfully titrated the fentanyl dosage required for pain control, and more than 90% did not require an increase in fentanyl dose to maintain pain control, Brooks said in his presentation at the European Society for Medical Oncology here.

"Fentanyl nasal spray is easily titrated to an effective dose across a broad range of opioid-tolerant cancer patients," said Brooks. "Only 8% of patients were unable to titrate because of reasons attributable to the fentanyl nasal spray."

Most cancer patients who experience pain also have breakthrough episodes. Breakthrough cancer pain is a distinct clinical entity that typically has a rapid onset with severe to excruciating intensity, resolving within an hour in most instances after treatment. However, such a lengthy period between treatment and the onset of pain relief can be agonizing for cancer patients.

Immediate-release morphine remains the standard treatment for most patients -- but it usually has an onset exceeding 30 minutes -- too slow for effective management of breakthrough cancer pain, Brooks commented.

Oral transmucosal formulations of fentanyl also have not met the need for rapid onset of action, and its use can be complicated by xerostomatitis and other oral problems common in advanced cancer.

Fentanyl pectin nasal spray was developed in an effort to optimize the drug's absorption profile, Brooks continued.

The pectin forms a thin gel layer on contact with calcium cations in the nasal mucosa, avoiding issues with runoff or swallowing, minimizing variable dosing related to drug loss.

Randomized controlled clinical trials have shown that fentanyl nasal spray provides pain relief superior to placebo and immediate-release morphine (Pain. 2010;epub, ESMO 09. Abstract LBA29). Brooks presented data from those two trials, plus a long-term open-label study that included patients from the randomized trials and from new patients with no prior exposure to fentanyl nasal spray.

The current analysis involved a total of 500 patients, 281 of whom were newly enrolled. Patients in the randomized trials were treated for as long as 21 days. During the open-label study, treatment continued for 16 days.

Patients were followed for as long as 14 days after the last dose of open-label therapy.

The primary outcomes were successful dose titration, consistency of effect, and safety and tolerability. Successful dose titration to a dose required to control two consecutive episodes of breakthrough cancer pain (100 to 800 µg).

Patients were allowed to take their usual pain medication if the pain did not subside within 30 minutes after treatment with fentanyl nasal spray.

Intranasal fentanyl pectin controlled most of episodes of breakthrough cancer pain. The most effective dose appeared to be 400 µg, with almost one-third of of patients controlled on that dose. Overall, 80.2% (401 of 500 patients) had successful titration of fentanyl nasal spray.

Brooks detailed the efficacy of four doses of the nasal spray:

7.7% of patients obtained pain control with an intranasal fentanyl dose of 100 µg.

21.8% of patients achieved control with a 200 µg of intranasal fentanyl.

32.0% of patients were controlled with 400 µg of fentanyl nasal spray.

28.5% of patients had pain control with 800 µg of fentanyl spray.

Patients achieved adequate pain relief with an average of 2.7 titration steps.

During the 16-week treatment phase of the open-label study, patients successfully treated 94% of 42,227 episodes of breakthrough cancer pain. When separated into four-week treatment intervals, success rates ranged from 93% to 95.1%.

Treatment-emergent adverse effects, including discontinuation, were consistent with known effects of fentanyl, including headache, nausea, and vomiting.

Treatment failure related to fentanyl consisted of adverse events in 3% of patients and lack of efficacy at the highest fentanyl dose in 5%.

Invited discussant Dorothy Keefe, MD, of the University of Adelaide in Australia, reiterated potential advantages of the nasal-spray formulation of fentanyl: rapid absorption, no first-pass metabolism, avoidance of problems involving the mouth or swallowing, controlled dosing, rapid onset, and good efficacy.

"This looks like a very good route of administration," remarked Keefe. "This route has potential for many other drugs."